The present invention relates to a novel vincamine derivative, namely vincamine saccharinate, and to pharmaceutical compositions containing this novel compound.
Vincamine is an alkaloid, isolated from Vinca minor L., which is well known to have pharmacological activity as a vasodilator and has been used for the treatment of cerebral circulatory and neurological disorders. Vincamine base is substantially insoluble in water and other pharmaceutically acceptable solvents and has been primarily administered orally in solid dosage forms, such as tablets or dragees. Vincamine has also been available, as the chlorohydrate salt, in solid form in ampoules for the preparation, by reconstitution with water, of dilute aqueous solutions, less than about 0.5% w/w, or suspensions, suitable for administration by injection.
A particular problem has been to find a form of vincamine, as a salt or other derivative, which is sufficiently soluble in a pharmaceutically acceptable solvent to provide a sufficient concentration of the drug in solution such that administration in solution form, preferably as drops, is possible, i.e. to provide the necessary dosage amount of the drug in an acceptably small volume of the solvent. In this regard, a further most significant problem has been that even the few salts or complexes of vincamine which have been found to be relatively soluble in pharmaceutically acceptable solvents, for example vincamine citrate or tartrate in glycerol-ethanol mixtures, and which would therefore provide an adequate concentration of the drug in solution, have an extremely bitter and unpleasant taste which has been impossible to mask or overcome by, for example, the addition of flavoring agents. The failure to find a form of vincamine that has both the desired solubility and acceptable taste characteristics has heretofore precluded the development of medicinally acceptable liquid pharmaceutical compositions for oral administration, especially of solutions having a sufficient concentration of the active drug that can be administered as drops. Accordingly, there has been a substantial need for a derivative of vincamine which provides relatively high solubility in a pharmaceutically acceptable solvent, but which does not have bitter or otherwise unpleasant taste characteristics.